Long-term evaluation of neurological outcomes in chemotherapy-associated posterior reversible encephalopathy (PRES) syndrome in children

Abstract

Background Posterior reversible encephalopathy syndrome (PRES) is a clinical syndrome with numerous etiologies, mostly characterized by magnetic resonance imaging (MRI) abnormalities in the posterior cerebral white and gray matter and acute neurological symptoms.

Aim To examine the predisposing factors, clinical results, and radiological features of PRES in children diagnosed with malignancy. Materials and

Methods The study included 20 patients (7 F/13 M) aged 4–16 years at the time of diagnosis who were diagnosed with malignancy and developed PRES during chemotherapy.

Results All the patients were diagnosed as having PRES both clinically and radiographically during chemotherapy. The time from the initiation of the chemotherapy to the onset of PRES ranged from 7–675 days. Hypertension was detected in nine patients, seizure was the most common presenting symptom – had involvement in the occipital and parietal lobes on MRI (n=14)/followed by headache (n=8)/altered consciousness (n=5)/visual impairment (n=4). Hydrocephalus and tentorial herniation were observed in one patient. Most of the lesions on MRI resolved within 10–33 days and the EEG findings within 9 months. Clinical symptoms of PRES also disappeared completely the 5-year Press frequency was found to be 2.48%.

Conclusion PRES may complicate the oncological treatment in children. Hypertension is a leading risk factor for PRES, while it should be kept in mind that the blood pressure may be normal in chemotherapy-induced PRES cases. PRES should be included in the differential diagnosis of all patients receiving chemotherapy and presenting with acute neurological symptoms.

Zusammenfassung

Das posteriore reversible Enzephalopathiesyndrom (PRES) ist ein klinisches Syndrom mit zahlreichen Ursachen, das meist durch Anomalien der Magnetresonanztomographie (MRT) in der hinteren weißen und grauen Substanz des Gehirns und akute neurologische Symptome gekennzeichnet ist. Untersuchung der prädisponierenden Faktoren, klinischen Ergebnisse und radiologischen Merkmale von PRES bei Kindern mit diagnostizierter Malignität. Die Studie umfasste 20 Patienten (7 F/13 M) im Alter von 4–16 Jahren zum Zeitpunkt der Diagnose, bei denen eine bösartige Erkrankung diagnostiziert wurde und die während der Chemotherapie PRES entwickelten. Bei allen Patienten wurde sowohl klinisch als auch radiologisch während der Chemotherapie PRES diagnostiziert. Die Zeitspanne vom Beginn der Chemotherapie bis zum Einsetzen von PRES lag zwischen 7 und 675 Tagen. Bei neun Patienten wurde Bluthochdruck festgestellt, Krampfanfälle waren das am häufigsten auftretende Symptom – mit Beteiligung der Hinterhaupts- und Scheitellappen im MRT (n=14)/gefolgt von Kopfschmerzen (n=8)/Bewusstseinsveränderungen (n=5)/Sehbehinderung (n=4). Bei einem Patienten wurden Hydrozephalus und Tentoriumherniation beobachtet. Die meisten Läsionen im MRT verschwanden innerhalb von 10–33 Tagen und die EEG-Befunde innerhalb von 9 Monaten. Die klinischen Symptome von PRES verschwanden ebenfalls vollständig; die 5-Jahres-Pressfrequenz betrug 2,48%. PRES kann die onkologische Behandlung bei Kindern erschweren. Bluthochdruck ist ein führender Risikofaktor für PRES, wobei zu bedenken ist, dass der Blutdruck in chemotherapiebedingten PRES-Fällen normal sein kann. PRES sollte in die Differentialdiagnose aller Patienten einbezogen werden, die eine Chemotherapie erhalten und akute neurologische Symptome aufweisen.

Keywords

posterior reversible encephalopathy (PRES) - chemotherapy-associated - children - neurological outcome

Schlüsselwörter

posteriore reversible Enzephalopathie (PRES) - Chemotherapie-assoziiert - kinder - neurologisches Ergebnis

Publikationsverlauf

Artikel online veröffentlicht:
20. Dezember 2024

• References

• 1 Hinchey J, Chaves C, Appignani B. et al. A Reversibl Posterior Leukoencephalopathy Syndrome. N Engl Med 1996; 334: 494-500
• 2 Incecik F, Hergüner MO, Altunbasak S. et al. Evaluation of nine children with reversible posterior encephalopathy syndrome. Neurology India 2009; 57: 475-478
• 3 Roth C, Ferbert A. The posterior reversible encephalopathy syndrome: what’s certain, what’s new?. Pract Neurol 2011; 11: 136-144
• 4 Hinchey J, Chaves C, Appignani B. et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494-500
• 5 Lamy C, Oppenheim C, Méder JF. et al. Neuroimaging in posterior reversible encephalopathy syndrome. J Neuroimaging 2004; 14: 89-96
• 6 Lucchini G, Grioni D, Colombini A. et al. Encephalopathy Syndrome in children with hemato-oncological disorders is not always posterior and reversible. Pediatr Blood Cancer 2008; 51: 629-633
• 7 Legriel S, Pico F, Azoulay E. Annual Update in Intensive Care and Emergency Medicine 2011. Understanding posterior reversible encephalopathy syndrome. Springer-Verlag; Berlin Heidelberg: 2011. pp 631-359
• 8 Floeter AE, Patel A, Tran M. et al. “Posterior Reversible Encephalopathy Syndrome Associated With Doseadjusted EPOCH (Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin) Chemotherapy.”. Clin Lymphoma Myeloma Leuk 2017; 17: 225-230
• 9 Teksam M, Casey SO, Michel E. et al. Posterior Reversibl Ensefalopati Sendromu: Patofizyoloji ve İleri MRG teknikleri ile korelasyon. Tanısal ve Girişimsel Radyoloji 2001; 7: 464-472
• 10 Pedraza R, Marik PE, Varon J. Posterior Reversible Encephalopathy Syndrome: A Review. Crit Care & Shock 2009; 12: 135-143
• 11 Alehan F, Erol I, Agildere AM. et al. Posterior leukoencephalopathy syndrome in children and adolescents. J Child Neurol 2007; 22: 406-413
• 12 Legriel S, Pico F, Azoulay E. Understanding Posterior Reversible Encephalopathy Syndrome. Annual Update in Intensive Care and Emergency Medicine 2011; 1: 631-653
• 13 Schwartz RB. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996; 334: 1743 Author reply 6.
• 14 Vaughn C, Zhang L, Schiff D. Reversible posterior leukoencephalopathy syndrome in cancer. Curr Oncol Rep 2008; 10: 86-91
• 15 Tam CS, Galanos J, Seymour JF. et al. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 2004; 77: 72-76
• 16 Bartynski WS, Boardman JF, Zeigler ZR. et al. Posterior reversible encephalopathy syndrome in infection, sepsis, and shock. AJNR Am J Neuroradiol 2006; 27: 2179-2190
• 17 Bartynski WS, Tan HP, Boardman JF. et al. Posterior reversible encephalopathy syndrome after solid organ transplantation. AJNR Am J Neuroradiol 2008; 29: 924-930
• 18 Fugate JE, Claassen DO, Cloft HJ. et al. Posterior reversible encephalopathy syndrome: associated clinical and radiologic findings. Mayo Clin Proc 2010; 85: 427-432
• 19 Legriel S, Pico F, Azoulay E. Understanding Posterior Reversible Encephalopathy Syndrome. Annual update in intensive care and emergency medicine. Springer; 2011. p. 631-653
• 20 Tam CS, Galanos J, Seymour JF. et al. Reversible Posterior Leukoencephalopathy Syndrome Complicating Cytotoxic Chemotherapyfor Hematologic Malignancies. Am J Hematol 2004; 77: 72-76
• 21 Tam CS, Galanos J, Seymour JF. et al. Reversible posterior leukoencephalopathy syndrome complicating cytotoxic chemotherapy for hematologic malignancies. Am J Hematol 2004; 77: 72-76
• 22 Liman TG, Bohner G, Heuschmann PU. et al. The clinical and radiological spectrum of posterior reversible encephalopathy syndrome: the retrospective Berlin PRES study. J Neurol 2012; 259: 155-164
• 23 Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 2008; 29: 1043-1049
• 24 Bracci L, Schiavoni G, Sistigu A. et al. Immune-based mechanisms of cytotoxic chemotherapy: implications for the design of novel and rationale-based combined treatments against cancer. Cell Death Differ 2014; 21: 15-25
• 25 Baethmann A, Maier-Hauff K, Kempski O. et al. Mediators of brain edema and secondary brain damage. Crit Care Med 1988; 16: 972-978
• 26 Stanimirovic D, Satoh K. Inflammatory mediators of cerebral endothelium: a role in ischemic brain inflammation. Brain Pathol 2000; 10: 113-126
• 27 Siebert E, Bohner G, Endres M. et al. Clinical and radiological spectrum of posterior reversible encephalopathy syndrome: does age make a difference? – A retrospective comparison between adult and pediatric patients. PLoS One 2014; 9: e115073
• 28 Bartynski WS. Posterior reversible encephalopathy syndrome, part 2: controversies surrounding pathophysiology of vasogenic edema. AJNR Am J Neuroradiol 2008; 29: 1043-1049
• 29 Morris EB, Laningham FH, Sandlund JT. et al. Posterior reversible encephalopathy syndrome in children with cancer. Pediatr Blood Cancer 2007; 48: 152-159
• 30 Kim SJ, Im SA, Lee JW. et al. Predisposing factors of posterior reversible encephalopathy syndrome in acute childhood leukemia. Pediatr Neurol 2012; 47: 436-442
• 31 Gümüş H, Per H, Kumandaş S. et al Reversible posterior leukoencephalopathy syndrome in childhood: report of nine cases and review of the literature. Neurol Sci 2010; 31: 125-131 Epub 2009 Oct.
• 32 Gupta A, Swaroop C, Rastogi R. et al. Simultaneous occurrence of posterior reversible leukoencephalopathy syndrome in two cases of childhood acute lymphoblastic leukemia induction chemotherapy. Pediatr Hematol Oncol 2008; 25: 351-358
• 33 Endo A, Fuchigami T, Hasegawa M. et al. Posterior reversible encephalopathy syndrome in childhood: report of four cases and review of the literature. Pediatr Emerg Care 2012; 28: 153-157
• 34 Pieters R, van den Heuvel-Eibrink MM. Posterior reversible encephalopathy syndrome in childhood cancer. Ann Oncol 2011; 22: 472-478
• 35 Lucchini G, Grioni D, Colombini A. et al. Encephalopathy Syndrome in children with hemato-oncological disorders is not always posterior and reversible. Pediatr Blood Cancer 2008; 51: 629-633
• 36 Khan RB, Sadighi ZS, Zabrowski J. et al. Imaging patterns and outcome of posterior reversible encephalopathy syndrome during childhood cancer treatment. Pediatr Blood Cancer 2016; 63: 523-526
• 37 Belaramani KM, Lai V, Li CH. et al. Reversible posterior leukoencephalopathy syndrome in Chinese children induced by chemotherapy: a review of five cases. Hong Kong Med J 2011; 17: 61-66
• 38 Won SC, Kwon SY, Han JW. et al. Posterior reversible encephalopathy syndrome in childhood with hematologic/oncologic diseases. J Pediatr Hematol Oncol 2009; 31: 505-508
• 39 Arzanian MT, BSh S, Karimzadeh P. et al. (2014 Spring) Posterior reversible encephalopathy syndrome in pediatric hematologic-oncologic disease: literature review and case presentation. Iran J Child Neurol 8: 1-10
• 40 D’Angelo P, Farruggia P, Lo Bello A. et al. Reversible posterior leukoencephalopathy syndrome: report of 2 simultaneous cases in children. J Pediatr Hematol Oncol 2006; 28: 177-181
• 41 Hualde Olascoaga J, Molins Castiella T, Souto Hernández S. et al. Reversible posterior leukoencephalopathy: report of two cases after vincristine treatment. An Pediatr (Barc). 2008. 68. 282-285
• 42 Kwon EJ, Kim SW, Kim KK. et al A case of gemcitabine and cisplatin associated posterior reversible encephalopathy syndrome. Cancer Res Treat 2009; 41: 53-55 Epub 2009 Mar 31.
• 43 Chemotherapy-associated posterior reversible encephalopathy syndrome: a case report and review of the literature. Neurologist. 21. 112-117
• 44 McKinney AM, Short J, Truwit CL. et al. Posterior reversible encephalopathy syndrome: incidence of atypical regions of involvement and imaging findings. AJR Am J Roentgenol 2007; 189: 904-991
• 45 Vieillot S, Pouessel D, de Champfleur NM. et al. Reversible posterior leukoencephalopathy syndrome after carboplatin therapy. Ann Oncol 2007; 18: 608-609
• 46 Saito B, Nakamaki T, Nakashima H. et al. Reversible posterior leukoencephalopathy syndrome after repeat intermediate-dose cytarabine chemotherapy in a patient with acute myeloid leukemia. Am J Hematol 2007; 82: 304-306
• 47 Bakshi R, Bates VE, Mechtler LL. et al. Occipital lobe seizures as the major clinical manifestation of reversible posterior leukoencephalopathy syndrome: magnetic resonance imaging findings. Epilepsia 1998; 39: 295-299
• 48 Yamada A, Ueda N. Age and gender may affect posterior reversible encephalopathy syndrome in renal disease. Pediatr Nephrol 2012; 27: 277-283
• 49 Raj S, Overby P, Erdfarb A. et al. Posterior reversible encephalopathy syndrome: incidence and associated factors in a pediatric critical care population. Pediatr Neurol 2013; 49: 335-339
• 50 Casey SO, Sampaio RC, Michel E. et al. Posterior reversible encephalopathy syndrome: utility of fluid-attenuated inversion recovery MR imaging in the detection of cortical and subcortical lesions. AJNR Am J Neuroradiol 2000; 21: 1199-1206
• 51 Donmez FY, Guleryuz P, Agildere M. MRI findings in childhood PRES: what is different than the adults?. Clin Neuroradiol. 2014